Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/199317
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | GM2-GM3 gangliosides ratio is dependent on GRP94 through down-regulation of GM2-AP cofactor in brain metastasis cells |
Autor: | Bedia, Carmen CSIC ORCID; Badia, Miriam; Muixí, Laia; Levade, Thierry; Tauler, Romà CSIC ORCID; Sierra, Àngels | Palabras clave: | Cancer cells Saposins GRP94 Sphingolipids |
Fecha de publicación: | 1-dic-2019 | Editor: | Springer Nature | Citación: | Scientific Reports 9 (1): 14241 (2019) | Resumen: | GRP94 is an ATP-dependent chaperone able to regulate pro-oncogenic signaling pathways. Previous studies have shown a critical role of GRP94 in brain metastasis (BrM) pathogenesis and progression. In this work, an untargeted lipidomic analysis revealed that some lipid species were altered in GRP94-deficient cells, specially GM2 and GM3 gangliosides. The catalytic pathway of GM2 is affected by the low enzymatic activity of β-Hexosaminidase (HexA), responsible for the hydrolysis of GM2 to GM3. Moreover, a deficiency of the GM2-activator protein (GM2-AP), the cofactor of HexA, is observed without alteration of gene expression, indicating a post-transcriptional alteration of GM2-AP in the GRP94-ablated cells. One plausible explanation of these observations is that GM2-AP is a client of GRP94, resulting in defective GM2 catabolic processing and lysosomal accumulation of GM2 in GRP94-ablated cells. Overall, given the role of gangliosides in cell surface dynamics and signaling, their imbalance might be linked to modifications of cell behaviour acquired in BrM progression. This work indicates that GM2-AP could be an important factor in ganglioside balance maintenance. These findings highlight the relevance of GM3 and GM2 gangliosides in BrM and reveal GM2-AP as a promising diagnosis and therapeutic target in BrM research. © 2019, The Author(s). | Versión del editor: | https://doi.org/10.1038/s41598-019-50761-5 | URI: | http://hdl.handle.net/10261/199317 | DOI: | 10.1038/s41598-019-50761-5 |
Aparece en las colecciones: | (IDAEA) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
GM2-GM3 gangliosides ratio is dependent on GRP94 through down-regulation of GM2-AP cofactor in brain metastasis cells.pdf | Artículo principal | 3,33 MB | Adobe PDF | Visualizar/Abrir |
Sup. Mat. GM2-GM3 gangliosides ratio is dependent on GRP94 through down-regulation of GM2-AP cofactor in brain metastasis cells.pdf | Material suplementario | 659,92 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
3
checked on 05-abr-2024
SCOPUSTM
Citations
6
checked on 17-abr-2024
WEB OF SCIENCETM
Citations
5
checked on 24-feb-2024
Page view(s)
164
checked on 23-abr-2024
Download(s)
324
checked on 23-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
Artículos relacionados:
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.